Acetylon Pharmaceuticals' Selective HDAC Inhibitor Programs to be Featured at the 54th Annual Meeting of the American Society of Hematology

BOSTON--(BUSINESS WIRE)--Nov 20, 2012 - Acetylon Pharmaceuticals
Inc., a leader in targeted epigenetic drug discovery and
development for enhanced therapeutic outcomes, today announced that
its selective histone deacetylase (HDAC) inhibitors will be
featured in five posters and one oral presentation at the
54th Annual Meeting of the American Society of
Hematology (ASH), taking place December 8-11, 2012, in Atlanta,
Georgia. These presentations will highlight three of Acetylon's
development programs: ACY-1215, a selective HDAC6 inhibitor
currently in two Phase 1b clinical trials for the treatment of
relapsed or relapsed/refractory multiple myeloma, preclinical
studies of ACY-1215 for the treatment of lymphoma, and a selective
HDAC1/2 inhibitor in preclinical studies for sickle cell disease
and beta-thalassemia.

“Acetylon is broadening its impact in epigenetic drug
discovery and development with the expansion of ACY-1215 into
lymphoma and the addition of an HDAC1/2 inhibitor in development
for sickle cell disease and beta-thalassemia,” said Walter C.
Ogier, President and Chief Executive Officer and co-founder of
Acetylon. “The lymphoma program is supported by three
presentations at ASH from leading academic research groups, who
demonstrate ACY-1215's synergistic effects with various other
anti-cancer drugs in preclinical studies of lymphoma. The potential
ability of ACY-1215 to enhance the activity of multiple anti-cancer
drugs in multiple myeloma and lymphoma is highly encouraging for
clinical development in these indications.”

Date: Monday, December 10, 2012Time: 6:00-8:00 pm ETLocation: Hall B1-B2Session: 653. Myeloma – Therapy, excluding
Transplantation: Poster IIIAbstract #: 4061Title:Rocilinostat (ACY-1215), a Selective HDAC6
Inhibitor, Alone and in Combination with Bortezomib in Multiple
Myeloma: Preliminary Results from the First-in-Humans Phase I/II
StudyAuthors Affiliated with the Following Institutions:
Massachusetts General Hospital, Medical College of Wisconsin,
University of Pennsylvania Perelman School of Medicine, Mount Sinai
School of Medicine, University of Texas MD Anderson Cancer Center,
Harvard Medical School, Rho Inc, Emory University and Acetylon
Pharmaceuticals Inc.Description: Preliminary results from this first clinical
evaluation of ACY-1215 suggest that selective inhibition of HDAC6
with ACY-1215, alone or in combination with bortezomib and
dexamethasone, may provide a well-tolerated treatment option for
relapsed or relapsed/refractory multiple myeloma.

Lymphoma

Date: Saturday, December 8, 2012Time: 5:30-7:30 pm ETLocation: Hall B1-B2Session: 625. Lymphoma – Pre-Clinical –
Chemotherapy and Biologic Agents: Poster IAbstract #: 1660Title:Combination of ACY-1215, a Selective Histone
Deacetylase 6 (HDAC6) Inhibitor with the Bruton Tyrosine Kinase
(BTK) Inhibitor, Ibrutinib, Represents a Novel Therapeutic Strategy
in Mantle Cell Lymphoma (MCL)Authors Affiliated with the Following Institutions: H. Lee
Moffitt Cancer Center & Research Institute, Weill Cornell
Medical College and Acetylon Pharmaceuticals Inc.Description: The viability of mantle cell lymphoma (MCL)
cells was decreased when they were treated in vitro with
either PCI-32765 or ACY-1215. However, combination of these two
agents resulted in a 3-fold increase in apoptosis induction,
pointing to a synergistic effect of BTK and HDAC6 inhibition in
MCL. The additional findings that this approach can increase the
immunogenicity of MCL cells and anti-MCL immune responses has
provided the proper framework for combining the selective HDAC6
inhibitor ACY-1215 with BTK inhibition as a novel therapeutic
strategy in MCL.

Date: Saturday, December 8, 2012Time: 5:30-7:30 pm ETLocation: Hall B1-B2Session: 625. Lymphoma – Pre-Clinical –
Chemotherapy and Biologic Agents: Poster IAbstract #: 1650Title:Dual Targeting of Protein Degradation Pathways
with the Selective HDAC6 Inhibitor Rocilinostat (ACY-1215) and
Bortezomib, Demonstrates Synergistic Antitumor Activity in
Preclinical Models of LymphomaAuthors Affiliated with the Following Institutions: Columbia
University Medical Center and Acetylon Pharmaceuticals Inc.Description: These are the first results to indicate that a
selective HDAC inhibitor can have marked activity across a panel of
lymphoma cell lines. These findings raise the prospect that dual
targeting of the ubiquitin-proteasome and aggressomal protein
degradation pathways can be synergistically effective. They provide
excellent pre-clinical rationale for expanding the use of ACY-1215
in combination with bortezomib for patients with relapsed or
refractory lymphoma.

Date: Sunday, December 9, 2012Time: 6:00-8:00 pm ETLocation: Hall B1-B2Session: 625. Lymphoma – Pre-Clinical –
Chemotherapy and Biologic Agents: Poster IIAbstract #: 2765Title:The Irreversible Proteasome Inhibitor Carfilzomib
Interacts Synergistically with the Selective HDAC6 Inhibitor
ACY-1215 in ABC- and GC-DLBCL and Mantle Cell Lymphoma Sensitive or
Resistant to BortezomibAuthors Affiliated with the Following Institutions: Virginia
Commonwealth University and University of RochesterDescription: These findings indicate that combining the
selective HDAC6 inhibitor ACY-1215 with carfilzomib (CFZ)
synergistically in preclinical models induces apoptosis in low- and
high-risk diffuse large B-cell lymphoma (DLBCL) and in mantle cell
lymphoma (MCL) cells through a JNK-dependent process in association
with G2M arrest, down-regulation of HR23B, and induction
of DNA damage. They also suggest that this strategy, which is
active against sensitive as well as bortezomib-resistant DLBCL and
MCL cells, warrants further exploration in NHL.

Blood cancers such as multiple myeloma and lymphoma are
characterized by successive genetic mutations resulting in
uncontrolled cell proliferation and dysfunctional production of
intracellular proteins. ACY-1215 selectively inhibits the
intracellular enzyme HDAC6, which leads to an accumulation of
excess protein and in addition may disrupt critical proliferative
signals in malignant cells. Disruption of these molecular processes
in cancer cells triggers programmed cell death, called "apoptosis,"
with little or no effect on normal cells. Currently available HDAC
drugs affect the expression of numerous genes in normal cells as
well as cancer cells, which can result in side effects such as
gastrointestinal dysfunction, lowered blood platelet levels and
risk of hemorrhage and profound fatigue as well as potential for
significant cardiac complications. Selective inhibition of HDAC6 is
expected to reduce or eliminate these often-severe side effects
associated with non-selective HDAC inhibition and may enable the
development of optimized treatment regimens, including maximally
effective combination drug therapies.

About HDAC1/2 Inhibition

The induction of fetal hemoglobin (HbF) is an established
therapeutic strategy for sickle cell disease and could potentially
also be effective for beta-thalassemia. HDAC inhibition has been
shown to induce HbF, however, clinical development of non-selective
HDAC inhibitors has been limited due to the number of off-target
side effects. Selective HDAC1/2 inhibition represents a novel
treatment approach that could represent a safer and more effective
treatment option for patients with sickle cell disease and
beta-thalassemia.

About Acetylon

Acetylon Pharmaceuticals Inc. is the leader in the development
of novel small molecule drugs targeting epigenetic mechanisms for
the enhanced therapeutic outcome of cancer and other critical unmet
medical needs. The Company's epigenetic drug discovery platform has
initially yielded a proprietary library of optimized,
orally-administered Class II histone deacetylase (HDAC)-selective
compounds. Restoration of proper HDAC regulation through
highly-selective HDAC inhibition is thought to be applicable to a
broad range of diseases, including cancer, sickle cell disease,
beta-thalassemia and autoimmune diseases. Acetylon's lead drug
candidate, ACY-1215, is a selective HDAC6 inhibitor in clinical
development for the treatment of multiple myeloma.